The Experts below are selected from a list of 1425 Experts worldwide ranked by ideXlab platform
Gregory Moeck - One of the best experts on this subject based on the ideXlab platform.
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In vitro stepwise selection of reduced susceptibility to Lipoglycopeptides in enterococci.
Diagnostic microbiology and infectious disease, 2017Co-Authors: Francis F. Arhin, Adam Belley, David Lalonde Seguin, Gregory MoeckAbstract:Abstract The propensity of oritavancin to select for stably elevated oritavancin minimum inhibitory concentrations (MICs) was studied by serial passaging of strains in broth containing oritavancin for 20days. Seven clinical strains of Enterococcus faecalis and E. faecium were studied; they included vancomycin-susceptible and both VanA and VanB vancomycin-resistant isolates. Stepwise oritavancin selection yielded stably elevated oritavancin MICs in six of the seven strains, with MIC increases ranging from 4–32-fold. By comparison, stepwise selection with comparator agents dalbavancin (4- to >128-fold MIC increases), telavancin (4–8-fold MIC increases) and daptomycin (4–32-fold MIC increases) also yielded selectants with elevated MICs of the respective agents. Oritavancin selectants retained parental MICs of vancomycin, daptomycin, linezolid and rifampicin. Some, but not all of the oritavancin selectants also showed MIC increases to the Lipoglycopeptides telavancin, dalbavancin and teicoplanin, suggesting that within the Lipoglycopeptide class, different mechanisms of action may be elucidated.
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1 Assessment of Oritavancin Serum Protein Binding across Species 1 2 Running title: Oritavancin Serum Protein Binding 3 4
2016Co-Authors: Francis F. Arhin, Adam Belley, Geoffrey Mckay, Sylvain Beaulieu, Ingrid Sarmiento, R. Parr, Gregory MoeckAbstract:2 Biophysical methods to study the binding of oritavancin, a Lipoglycopeptide, to serum 23 protein are confounded by nonspecific drug adsorption to labware surfaces. We assessed 24 oritavancin binding to serum from mouse, rat, dog and human by a microbiological growth-25 based method under conditions that allow near-quantitative drug recovery. Protein binding was 26 similar across species, ranging from 81.9 % in human serum to 87.1 % in dog serum. These 27 estimates support translation of oritavancin exposure from nonclinical studies to humans.28 3 Estimates of serum protein binding are essential to translate drug exposure from nonclinical 29 species to humans during assessments of toxicology, pharmacokinetics, and pharmacodynamics 30 since the free fraction dictates drug activity (3, 17, 18). Recent evidence supports the concept of 31 an “active fraction ” that offers insight into the pharmacodynamic behavior of highly protein-32 bound drugs such as daptomycin (20). 33 Oritavancin is a late-stage investigational Lipoglycopeptide under study for treatment of 34 serious gram-positive infections (6). Nonspecific binding of oritavancin to labware surfaces (1,2) 3
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Glycopeptides and Lipoglycopeptides
Antibiotic Discovery and Development, 2011Co-Authors: Francis F. Arhin, Adam Belley, Gregory Moeck, A. Rafai Far, Dario Lehoux, Thomas R. ParrAbstract:The scourge of resistance to antibacterial agents is a global problem of increasing severity. A recent review by Boucher and colleagues [33] summarized the alarming viewpoint of the Infectious Diseases Society of America (IDSA) that a stagnated development pipeline combined with continuing evolution of resistance, including emergence of pan-resistant strains, foretells of continued escalating healthcare costs and little reason for optimism in countering resistance to antibacterial agents.
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Oritavancin Disrupts Membrane Integrity of Staphylococcus aureus and Vancomycin-Resistant Enterococci To Effect Rapid Bacterial Killing
Antimicrobial agents and chemotherapy, 2010Co-Authors: Adam Belley, Francis F. Arhin, Geoffrey A. Mckay, Thomas R. Parr, Sylvain Beaulieu, Ingrid Sarmiento, Ibthihal Fadhil, Gregory MoeckAbstract:Oritavancin is an investigational Lipoglycopeptide in clinical development for the treatment of acute bacterial skin and skin structure infections. In this study, we demonstrate that oritavancin causes bacterial membrane depolarization and permeabilization leading to cell death of Gram-positive pathogens and that these effects are attributable to the 4′-chlorobiphenylmethyl group of the molecule.
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characterization of the in vitro activity of novel Lipoglycopeptide antibiotics
Current protocols in microbiology, 2010Co-Authors: Francis F. Arhin, Adam Belley, Geoffrey A. Mckay, Gregory MoeckAbstract:The increasing incidence of antibiotic resistance in human pathogens is of significant concern. Resistance to the widely-used and highly effective glycopeptide antibacterial agent vancomycin, which has been in clinical use for over half a century, has emerged in staphylococci and enterococci. This has spurred the development of newer glycopeptide agents, some of which show activity against vancomycin-resistant organisms. The newer agents currently being developed contain lipophilic side-chains, which distinguish them from vancomycin; as such, they are categorized as Lipoglycopeptides. Oritavancin, telavancin, and dalbavancin are Lipoglycopeptides in late-stage development to combat Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. This unit describes methods that may be used to assess the in vitro activities of Lipoglycopeptides. The methods include susceptibility assays, time-kill and time-kill-synergy assays, inhibition of synthesis of macromolecules, membrane perturbation assays, and measurement of activity against biofilms. Curr. Protoc. Microbiol. 16:17.1.1-17.1.22. © 2010 by John Wiley & Sons, Inc. Keywords: oritavancin; Lipoglycopeptide; broth microdilution; time-kill; synergy; biofilm; macromolecular synthesis
Adam Belley - One of the best experts on this subject based on the ideXlab platform.
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In vitro stepwise selection of reduced susceptibility to Lipoglycopeptides in enterococci.
Diagnostic microbiology and infectious disease, 2017Co-Authors: Francis F. Arhin, Adam Belley, David Lalonde Seguin, Gregory MoeckAbstract:Abstract The propensity of oritavancin to select for stably elevated oritavancin minimum inhibitory concentrations (MICs) was studied by serial passaging of strains in broth containing oritavancin for 20days. Seven clinical strains of Enterococcus faecalis and E. faecium were studied; they included vancomycin-susceptible and both VanA and VanB vancomycin-resistant isolates. Stepwise oritavancin selection yielded stably elevated oritavancin MICs in six of the seven strains, with MIC increases ranging from 4–32-fold. By comparison, stepwise selection with comparator agents dalbavancin (4- to >128-fold MIC increases), telavancin (4–8-fold MIC increases) and daptomycin (4–32-fold MIC increases) also yielded selectants with elevated MICs of the respective agents. Oritavancin selectants retained parental MICs of vancomycin, daptomycin, linezolid and rifampicin. Some, but not all of the oritavancin selectants also showed MIC increases to the Lipoglycopeptides telavancin, dalbavancin and teicoplanin, suggesting that within the Lipoglycopeptide class, different mechanisms of action may be elucidated.
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1 Assessment of Oritavancin Serum Protein Binding across Species 1 2 Running title: Oritavancin Serum Protein Binding 3 4
2016Co-Authors: Francis F. Arhin, Adam Belley, Geoffrey Mckay, Sylvain Beaulieu, Ingrid Sarmiento, R. Parr, Gregory MoeckAbstract:2 Biophysical methods to study the binding of oritavancin, a Lipoglycopeptide, to serum 23 protein are confounded by nonspecific drug adsorption to labware surfaces. We assessed 24 oritavancin binding to serum from mouse, rat, dog and human by a microbiological growth-25 based method under conditions that allow near-quantitative drug recovery. Protein binding was 26 similar across species, ranging from 81.9 % in human serum to 87.1 % in dog serum. These 27 estimates support translation of oritavancin exposure from nonclinical studies to humans.28 3 Estimates of serum protein binding are essential to translate drug exposure from nonclinical 29 species to humans during assessments of toxicology, pharmacokinetics, and pharmacodynamics 30 since the free fraction dictates drug activity (3, 17, 18). Recent evidence supports the concept of 31 an “active fraction ” that offers insight into the pharmacodynamic behavior of highly protein-32 bound drugs such as daptomycin (20). 33 Oritavancin is a late-stage investigational Lipoglycopeptide under study for treatment of 34 serious gram-positive infections (6). Nonspecific binding of oritavancin to labware surfaces (1,2) 3
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Glycopeptides and Lipoglycopeptides
Antibiotic Discovery and Development, 2011Co-Authors: Francis F. Arhin, Adam Belley, Gregory Moeck, A. Rafai Far, Dario Lehoux, Thomas R. ParrAbstract:The scourge of resistance to antibacterial agents is a global problem of increasing severity. A recent review by Boucher and colleagues [33] summarized the alarming viewpoint of the Infectious Diseases Society of America (IDSA) that a stagnated development pipeline combined with continuing evolution of resistance, including emergence of pan-resistant strains, foretells of continued escalating healthcare costs and little reason for optimism in countering resistance to antibacterial agents.
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Oritavancin Disrupts Membrane Integrity of Staphylococcus aureus and Vancomycin-Resistant Enterococci To Effect Rapid Bacterial Killing
Antimicrobial agents and chemotherapy, 2010Co-Authors: Adam Belley, Francis F. Arhin, Geoffrey A. Mckay, Thomas R. Parr, Sylvain Beaulieu, Ingrid Sarmiento, Ibthihal Fadhil, Gregory MoeckAbstract:Oritavancin is an investigational Lipoglycopeptide in clinical development for the treatment of acute bacterial skin and skin structure infections. In this study, we demonstrate that oritavancin causes bacterial membrane depolarization and permeabilization leading to cell death of Gram-positive pathogens and that these effects are attributable to the 4′-chlorobiphenylmethyl group of the molecule.
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characterization of the in vitro activity of novel Lipoglycopeptide antibiotics
Current protocols in microbiology, 2010Co-Authors: Francis F. Arhin, Adam Belley, Geoffrey A. Mckay, Gregory MoeckAbstract:The increasing incidence of antibiotic resistance in human pathogens is of significant concern. Resistance to the widely-used and highly effective glycopeptide antibacterial agent vancomycin, which has been in clinical use for over half a century, has emerged in staphylococci and enterococci. This has spurred the development of newer glycopeptide agents, some of which show activity against vancomycin-resistant organisms. The newer agents currently being developed contain lipophilic side-chains, which distinguish them from vancomycin; as such, they are categorized as Lipoglycopeptides. Oritavancin, telavancin, and dalbavancin are Lipoglycopeptides in late-stage development to combat Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. This unit describes methods that may be used to assess the in vitro activities of Lipoglycopeptides. The methods include susceptibility assays, time-kill and time-kill-synergy assays, inhibition of synthesis of macromolecules, membrane perturbation assays, and measurement of activity against biofilms. Curr. Protoc. Microbiol. 16:17.1.1-17.1.22. © 2010 by John Wiley & Sons, Inc. Keywords: oritavancin; Lipoglycopeptide; broth microdilution; time-kill; synergy; biofilm; macromolecular synthesis
Francis F. Arhin - One of the best experts on this subject based on the ideXlab platform.
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In vitro stepwise selection of reduced susceptibility to Lipoglycopeptides in enterococci.
Diagnostic microbiology and infectious disease, 2017Co-Authors: Francis F. Arhin, Adam Belley, David Lalonde Seguin, Gregory MoeckAbstract:Abstract The propensity of oritavancin to select for stably elevated oritavancin minimum inhibitory concentrations (MICs) was studied by serial passaging of strains in broth containing oritavancin for 20days. Seven clinical strains of Enterococcus faecalis and E. faecium were studied; they included vancomycin-susceptible and both VanA and VanB vancomycin-resistant isolates. Stepwise oritavancin selection yielded stably elevated oritavancin MICs in six of the seven strains, with MIC increases ranging from 4–32-fold. By comparison, stepwise selection with comparator agents dalbavancin (4- to >128-fold MIC increases), telavancin (4–8-fold MIC increases) and daptomycin (4–32-fold MIC increases) also yielded selectants with elevated MICs of the respective agents. Oritavancin selectants retained parental MICs of vancomycin, daptomycin, linezolid and rifampicin. Some, but not all of the oritavancin selectants also showed MIC increases to the Lipoglycopeptides telavancin, dalbavancin and teicoplanin, suggesting that within the Lipoglycopeptide class, different mechanisms of action may be elucidated.
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1 Assessment of Oritavancin Serum Protein Binding across Species 1 2 Running title: Oritavancin Serum Protein Binding 3 4
2016Co-Authors: Francis F. Arhin, Adam Belley, Geoffrey Mckay, Sylvain Beaulieu, Ingrid Sarmiento, R. Parr, Gregory MoeckAbstract:2 Biophysical methods to study the binding of oritavancin, a Lipoglycopeptide, to serum 23 protein are confounded by nonspecific drug adsorption to labware surfaces. We assessed 24 oritavancin binding to serum from mouse, rat, dog and human by a microbiological growth-25 based method under conditions that allow near-quantitative drug recovery. Protein binding was 26 similar across species, ranging from 81.9 % in human serum to 87.1 % in dog serum. These 27 estimates support translation of oritavancin exposure from nonclinical studies to humans.28 3 Estimates of serum protein binding are essential to translate drug exposure from nonclinical 29 species to humans during assessments of toxicology, pharmacokinetics, and pharmacodynamics 30 since the free fraction dictates drug activity (3, 17, 18). Recent evidence supports the concept of 31 an “active fraction ” that offers insight into the pharmacodynamic behavior of highly protein-32 bound drugs such as daptomycin (20). 33 Oritavancin is a late-stage investigational Lipoglycopeptide under study for treatment of 34 serious gram-positive infections (6). Nonspecific binding of oritavancin to labware surfaces (1,2) 3
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Glycopeptides and Lipoglycopeptides
Antibiotic Discovery and Development, 2011Co-Authors: Francis F. Arhin, Adam Belley, Gregory Moeck, A. Rafai Far, Dario Lehoux, Thomas R. ParrAbstract:The scourge of resistance to antibacterial agents is a global problem of increasing severity. A recent review by Boucher and colleagues [33] summarized the alarming viewpoint of the Infectious Diseases Society of America (IDSA) that a stagnated development pipeline combined with continuing evolution of resistance, including emergence of pan-resistant strains, foretells of continued escalating healthcare costs and little reason for optimism in countering resistance to antibacterial agents.
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Oritavancin Disrupts Membrane Integrity of Staphylococcus aureus and Vancomycin-Resistant Enterococci To Effect Rapid Bacterial Killing
Antimicrobial agents and chemotherapy, 2010Co-Authors: Adam Belley, Francis F. Arhin, Geoffrey A. Mckay, Thomas R. Parr, Sylvain Beaulieu, Ingrid Sarmiento, Ibthihal Fadhil, Gregory MoeckAbstract:Oritavancin is an investigational Lipoglycopeptide in clinical development for the treatment of acute bacterial skin and skin structure infections. In this study, we demonstrate that oritavancin causes bacterial membrane depolarization and permeabilization leading to cell death of Gram-positive pathogens and that these effects are attributable to the 4′-chlorobiphenylmethyl group of the molecule.
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characterization of the in vitro activity of novel Lipoglycopeptide antibiotics
Current protocols in microbiology, 2010Co-Authors: Francis F. Arhin, Adam Belley, Geoffrey A. Mckay, Gregory MoeckAbstract:The increasing incidence of antibiotic resistance in human pathogens is of significant concern. Resistance to the widely-used and highly effective glycopeptide antibacterial agent vancomycin, which has been in clinical use for over half a century, has emerged in staphylococci and enterococci. This has spurred the development of newer glycopeptide agents, some of which show activity against vancomycin-resistant organisms. The newer agents currently being developed contain lipophilic side-chains, which distinguish them from vancomycin; as such, they are categorized as Lipoglycopeptides. Oritavancin, telavancin, and dalbavancin are Lipoglycopeptides in late-stage development to combat Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. This unit describes methods that may be used to assess the in vitro activities of Lipoglycopeptides. The methods include susceptibility assays, time-kill and time-kill-synergy assays, inhibition of synthesis of macromolecules, membrane perturbation assays, and measurement of activity against biofilms. Curr. Protoc. Microbiol. 16:17.1.1-17.1.22. © 2010 by John Wiley & Sons, Inc. Keywords: oritavancin; Lipoglycopeptide; broth microdilution; time-kill; synergy; biofilm; macromolecular synthesis
David P. Nicolau - One of the best experts on this subject based on the ideXlab platform.
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Clinical pathway for moderate to severe acute bacterial skin and skin structure infections from a US perspective: a roundtable discussion
Hospital practice (1995), 2016Co-Authors: John A. Bosso, David P. Nicolau, Anthony M. Casapao, Jonathan Edwards, Kenneth P. Klinker, Christopher Mccoy, Katherine K. Perez, Andrew Marcarelli, Deeksha DuaAbstract:This article was written with the aim to establish a consensus clinical pathway for long-acting Lipoglycopeptide antibiotics such as oritavancin (Orbactiv®) and dalbavancin (Dalvance®) for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Seven infectious diseases pharmacy specialists from a variety of facilities across the United States (US) participated in a roundtable discussion to consider the use of newer single-dose long-acting Lipoglycopeptides, and integrate them into clinical pathways for ABSSSI. They identified two ways of treating with these drugs: first, to facilitate discharge from the hospital by switching from initial therapy (e.g., with intravenous (IV) vancomycin) and second, to avoid hospital admission altogether, since the product can be administered in several outpatient settings of care including the emergency department (ED), observation unit (OU) or outpatient infusion center. The participants used existing literature on classification and treatment of ABSSSI and their experience in the clinical setting as bases for their discussion and came to a consensus on the considerations for patient inclusion and exclusion as well as a pathway for outpatient treatment with long-acting Lipoglycopeptides. As a result of the discussion, we concluded that the current treatment paradigm for ABSSSI is ripe for re-evaluation and reconfiguration in order to more closely align with the changing healthcare landscape. Hospital stakeholders are constantly searching for new strategies that can improve quality of care while simultaneously reducing overall expenses. The availability of single-dose long-acting Lipoglycopeptides is an opportunity to opt for lower-cost outpatient treatment of appropriate ABSSSI patients. This article proposes the inclusion and exclusion considerations, along with a consensus treatment pathway, that could provide a solid foundation for facilities to construct and adapt their own effective clinical pathways for ABSSSI.
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Review of dalbavancin, a novel semisynthetic Lipoglycopeptide
Expert opinion on investigational drugs, 2007Co-Authors: Aryun Kim, Joseph L. Kuti, David P. NicolauAbstract:Dalbavancin is a semisynthetic Lipoglycopeptide that is derived from teicoplanin with an extended half-life that enables once-weekly dosing. It has potent in vitro activity against most gram-positive organisms, with lower minimum inhibitory concentration values than vancomycin and other investigational Lipoglycopeptides. Dalbavancin is active against multi-drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, except for strains exhibiting vanA resistance. Several Phase II and III trials have established similar efficacy and safety of dalbavancin with comparator agents in the treatment of complicated skin and skin structure infections and in catheter-related bloodstream infections. Dalbavancin may serve as an appealing alternative agent in the treatment of gram-positive infections, especially with its convenient once-weekly regimen.
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Telavancin: a novel Lipoglycopeptide for serious gram-positive infections.
Expert opinion on investigational drugs, 2007Co-Authors: Somvadee Laohavaleeson, Joseph L. Kuti, David P. NicolauAbstract:Telavancin, a once-daily dosing Lipoglycopeptide derived from vancomycin, has a broad-spectrum microbiologic activity against gram-positive bacteria, including vancomycin-resistant staphylococci. Telavancin displays a dual mode of action and a rapid bactericidal killing. The in vitro activity of telavancin is superior to vancomycin and comparable with, or greater than, linezolid, daptomycin and other novel Lipoglycopeptides. Telavancin is effective against gram-positive pathogens in animal models of soft tissue infections and deep-seated infections including endocarditis, pneumonia and bacteremia. Clinical experience with telavancin in Phase II and III studies for complicated skin and skin structure infections have demonstrated similar efficacy and tolerability compared with standard anti-staphylococcal beta-lactams and vancomycin. Telavancin is in Phase III studies for nosocomial pneumonia. Telavancin seems to be promising as a novel agent for empiric therapy or as an alternative agent in serious infections caused by clinically important resistant gram-positive pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin intermediate-susceptible S. aureus, vancomycin-resistant S. aureus and vancomycin-resistant enterococci.
Martin E. Stryjewski - One of the best experts on this subject based on the ideXlab platform.
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Bacteremic nosocomial pneumonia cases from the ATTAIN studies
Critical Care, 2010Co-Authors: Ethan Rubinstein, Steven L Barriere, G. R. Corey, Fc Genter, Carlos M. Luna, A Lentnek, Martin E. StryjewskiAbstract:Bacteremic pneumonia is associated with worse outcome including higher mortality. The ATTAIN program compared telavancin (TLV), a Lipoglycopeptide antibiotic, with vancomycin (VAN) for treatment of nosocomial pneumonia (NP) due to Gram-positive pathogens including MRSA. This subgroup analysis examined the baseline characteristics and clinical outcomes in bacteremic HAP cases.
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A new Lipoglycopeptide: telavancin.
Expert opinion on pharmacotherapy, 2008Co-Authors: Esteban C. Nannini, Martin E. StryjewskiAbstract:The increase in infections caused by resistant Gram-positive organisms has led to an urgent need for new antibiotics. Telavancin is a rapidly bactericidal Lipoglycopeptide with multiple mechanisms of action, including concentration-dependent inhibition of bacterial cell wall synthesis and disruption of the functional integrity of the cell membrane. Telavancin is active against a wide variety of Gram-positive organisms including Staphylococcus aureus with resistance to methicillin, reduced susceptibility to vancomycin, and full resistance to vancomycin. Telavacin is approximately 90% protein bound; it has a serum half-life of around 8 h and a prolonged postantibiotic effect, allowing once daily administration. Telavancin is eliminated principally through the urine, requiring dose adjustment in patients with renal impairment. The efficacy and safety of telavancin was demonstrated in a large program of patients with complicated skin and skin structure infections. Development of resistance has not been detect...
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Efficacy of telavancin for treatment of surgical site infections
Critical Care, 2008Co-Authors: Samuel E. Wilson, Steven L Barriere, Martin E. Stryjewski, Vance G. Fowler, David J. Young, F Jacobs, A. Hopkins, Michael M. Kitt, G. R. CoreyAbstract:The purpose of this study was to evaluate the efficacy of telavancin (TLV), a novel bactericidal Lipoglycopeptide with a multifunctional mechanism of action, for the treatment of surgical site infections due to Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).